1. Field of the Invention
This invention relates to an interferon-inducing complex, and more particularly, to a nuclease-resistant hydrophilic complex of polyriboinosinic-polyribocytidylic acid useful for inducing the synthesis of interferon in primates, including non-human primates.
2. Description of the Prior Art
The synthetic double-stranded RNA, polyriboinosinic-polyribocytidylic acid (hereinafter "In.Cn") is a material known for its activity as an interferon inducer, antiviral, and antitumor agent in rodents. This material, the method for its preparation, and its aforementioned activity in rodents, are described, for example, by Field, et al., Proceedings of the National Academy of Sciences, Volume 58, Pages 1004-1010 (1967), and Levy, et al., Proceedings of the National Academy of Sciences, Volume 62, No. 2, pages 357-361 (1969). In man, however, In.Cn has proven to be a poor interferon inducer and has no detectable antitumor action. There is present in human serum a high level of hydrolytic activity against In.Cn which conceivably could be responsible for the low activity of the drug in man. Although several attempts have been made to prepare stabilized In.Cn derivatives, none of these compounds has proved to be fruitful. Moreover, previous attempts have been made to induce interferon in non-human primates with In.Cn, but little or no interferon was produced. While in man and non-human primates topical application has had some very minor success in prophylaxis of some viral diseases, there has been no success in altering the course of systemic clinical disease with interferon inducers.
In connection with its activity in rodents, In.Cn of relatively low molecular weight, i.e., within the range from about 1.times.10.sup.5 to about 3.times.10.sup.5 daltons, has previously been found to have its activity enhanced by complexing it with high molecular weight poly-d-lysine, i.e., having a molecular weight of approximately 180,000 daltons. It was not possible, however, to use the same procedure with a high molecular weight In.Cn, i.e., having a molecular weight within the range of from about 7.times.10.sup.5 to about 1.times.10.sup.7 daltons. Further, since the amino acid, d-lysine, is not a natural occurring amino acid, it was felt that high molecular weight poly-d-lysine would very likely be restrictively antigenic.
In U.S. Pat. Nos. 3,952,097 and 4,024,241, and various corresponding foreign patents claiming priority therefrom, of all of which I am also the sole inventor, there are described and claimed similar complexes to that of the present invention, and the use of said compounds. However, in all of these patents, the poly-1-lysine component of the complex is disclosed as having a molecular weight range of from about 2,000 daltons to about 5,000 daltons. After further research and development, it has now unexpectedly been found that the complexes disclosed and claimed in these patents are inoperative. Apparently, the supplier of the poly-1-lysine used in the original research mislabeled the molecular weight range of the supplied compound. This was discovered after attempts to replicate the original experimentation with poly-1-lysine having a true molecular weight of about 2,000 to about 5,000 daltons were unsuccessful.